A direct synthesis of 1-aryl- and 1-alkenylcyclopropylamines from aryl and alkenyl nitriles

Article abstract of DOI:10.1021/jo034710+

The reaction of various aromatic nitriles with 1.1 equiv of Ti(Oi-Pr)4 and 2.2 equiv of EtMgBr followed by addition of a Lewis acid gave 1-aryl cyclopropylamines in 43-76% yields. Under similar conditions, conjugated alkene-nitriles afford 1-alkenylcyclopropylamines (42-65%).

Full text of DOI:10.1021/jo034710+

SCHEME 1
A Dir ect Syn th esis of 1-Ar yl- a n d
1-Alk en ylcyclop r op yla m in es fr om Ar yl a n d
Alk en yl Nitr iles
Philippe Bertus* and J an Szymoniak
SCHEME 2
CNRS UMR 6519, Re´actions Se´lectives et Applications,
Universite´ de Reims-Champagne-Ardenne, BP 1039,
51687 Reims Cedex 2, France
philippe.bertus@univ-reims.fr
Received May 26, 2003
Abstr a ct: The reaction of various aromatic nitriles with
1.1 equiv of Ti(Oi-Pr)4 and 2.2 equiv of EtMgBr followed by
addition of a Lewis acid gave 1-aryl cyclopropylamines in
43-76% yields. Under similar conditions, conjugated alkene-
nitriles afford 1-alkenylcyclopropylamines (42-65%).
Meijere et al. proposed very recently a new method
for preparing 1-arylcyclopropylamines from aromatic
nitriles, by using diethylzinc and MeTi(Oi-Pr)3 in the
presence of lithium salts (i-PrOLi and LiI).8 The yields
obtained by this method are fair to good, depending on
the substitution on the aromatic ring. These results led
us to propose here our own solution of this problem
through organomagnesium-based chemistry.
First, the optimization of the reaction was performed
with benzonitrile (Scheme 2). When ethylmagnesium
bromide was added to a solution of the nitrile and
titanium isopropoxide in ether, only a small quantity of
cyclopropylamine product 3a was formed (15% yield)
after 1 h, the main product being propiophenone (2, 31%).
Letting the reaction continue longer (20 h) did not favor
the formation of 3a . However, the addition of a Lewis
acid (BF3‚OEt2) to the reaction mixture before hydrolysis
increases significantly the yield of cyclopropylamine
(47%). As for aliphatic nitriles, the role of the Lewis acid
is important in the cyclization step leading to cyclopro-
pane.
The yield of cyclopropylamine was further increased
when modifying the experimental procedure. Most im-
portantly, ethylmagnesium bromide (2.2 equiv) was
added at lower temperature (-70 °C) before the reaction
mixture was warmed to room temperature.9 1-Phenyl-
cyclopropylamine (3a ) was thus obtained in good yield
(65%), similar to that obtained by the de Meijere proce-
dure (62%).8 Modification of these optimized conditions
by the use of substoichiometric quantities of titanium
alkoxide (0.2 equiv) or an excess of Grignard reagent
(3 equiv) led to the total disappearance of the cyclopro-
pylamine.
Aminocyclopropane moiety is frequently found in nu-
merous biologically active substances such as natural
amino acids1 and synthetic drugs.2 Recently, we proposed
a method of preparing primary cyclopropylamines from
aliphatic nitriles,3 by the use of titanium isopropoxide
and a Grignard reagent, and subsequent addition of a
Lewis acid (Scheme 1). This reaction can be considered
as an extension of the zirconium-mediated synthesis of
cyclopropanes from carbonyl compounds.4 It is related to
the Kulinkovich5 and de Meijere6 conversions of esters
and tertiary amides to cyclopropanols and tertiary cy-
clopropylamines, respectively.7
However, primary 1-arylcyclopropylamines were not
accessible in good yield from aryl cyanides or amides by
the above procedures.3a,8 To overcome this problem, de
(1) Pirrung, M. C. Acc. Chem. Res. 1999, 32, 711-718.
(2) See for example: (a) Koglin, N.; Zorn, C.; Beumer, R.; Cabrele,
C.; Bubert, C.; Sewald, N.; Reiser, O.; Beck-Sickinger, A.-G. Angew.
Chem., Int. Ed. 2003, 42, 202-205. 1-Arylcyclopropylamines as
drugs: (b) Todo, Y.; Nitta, J .; Miyajima, M.; Fukuoka, Y.; Yamashiro,
Y.; Nishida, N.; Saikawa, I.; Narita, H. Chem. Pharm. Bull. 1994, 42,
2063. (c) Hanano, T.; Adachi, K.; Aoki, Y.; Morimoto, H.; Naka, Y.;
Hisadome, M.; Fukuda, T.; Sumichika, H. Bioorg. Med. Chem. Lett.
2000, 10, 881-884.
(3) (a) Bertus, P.; Szymoniak, J . Chem. Commun. 2001, 1792-1793.
(b) Bertus, P.; Szymoniak, J . J . Org. Chem. 2002, 67, 3965-3968. (c)
Bertus, P.; Szymoniak, J . Synlett 2003, 265-267. (d) Laroche, C.;
Bertus, P.; Szymoniak, J . Tetrahedron Lett. 2003, 44, 2485-2487.
(4) (a) Bertus, P.; Gandon, V.; Szymoniak, J . Chem. Commun. 2000,
171-172. (b) Gandon, V.; Bertus, P.; Szymoniak, J . Eur. J . Org. Chem.
2000, 3713-3719.
(5) (a) Kulinkovich, O. G.; Sviridov, S. V.; Vasilevsky, D. A.;
Prityckaja, T. S. Zh. Org. Khim. 1989, 25, 2244-2245. (b) Kulinkovich,
O. G.; Sviridov, S. V.; Vasilevsky, D. A. Synthesis 1991, 234. (c) See
also: Lee, J .; Kim, H.; Cha, J . K. J . Am. Chem. Soc. 1996, 118, 4198-
4199.
(6) (a) Chaplinski, V.; de Meijere, A. Angew. Chem., Int. Ed. Engl.
1996, 35, 413-414. (b) Chaplinski, V.; Winsel, H.; Kordes, M.; de
Meijere, A. Synlett 1997, 111-114. (c) Kordes, M.; Winsel, H.; de
Meijere, A. Eur. J . Org. Chem. 2000, 3235-3245. (d) See also: Lee,
J .; Cha, J . K. J . Org. Chem. 1997, 62, 1584-1585.
This procedure for the conversion of substituted aro-
matic nitriles10 to 1-arylcyclopropylamines appears to be
(9) Similarly, the Kulinkovich conversion of aromatic esters to aryl
cyclopropanols is best performed when the reagents are mixed at low
temperature, and warmed afterwards to 0 °C. See: Kulinkovich, O.
G.; Sviridov, S. V.; Vasilevskii, D. A.; Savchenko, A. I.; Pritytskaya, T.
S. Zh. Org. Khim. 1991, 27, 294-298; J . Org. Chem. USSR 1991, 27,
250-253.
(10) Nitriles 1b-f, 1h , 1k , and 6a -e were conveniently prepared
in good yields from the corresponding aldehydes by action of I2/NH4-
OH. See: Talukdar, S.; Hsu, J .-L.; Chou, T.-C.; Fang, J .-M. Tetrahedron
Lett. 2001, 42, 1103-1105.
(7) Reviews: (a) de Meijere, A.; Kulinkovich, O. G. Chem. Rev. 2000,
100, 2789-2834. (b) Sato, F.; Urabe, H.; Okamoto, S. Chem. Rev. 2000,
100, 2835-2886. (c) de Meijere, A.; Koshushkov, S. I.; Savchenko, A.
I. In Titanium and Zirconium in Organic Synthesis; Marek, I., Ed.;
Wiley-VCH: Weinheim, Germany, 2002; pp 390-434.
(8) Wiedemann, S.; Frank, D.; Winsel, H.; de Meijere, A. Org. Lett.
2003, 5, 753-755.
10.1021/jo034710+ CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/13/2003
J . Org. Chem. 2003, 68, 7133-7136
7133

TABLE 1. P r ep a r a tion of 1-Ar ylcyclop r op yla m in es
TABLE 2. P r ep a r a tion of 1-Alk en ylcyclop r op yla m in es
a
Isolated yields.
1-Alkenylcyclopropylamines contain both vinylcyclo-
propane and cyclopropylamine moieties. Despite their
great synthetic potential, only a few syntheses of vinyl-
cyclopropylamines have been reported.13,14 These com-
pounds were mostly used as intermediates for the
synthesis of 2,3-methanoamino acids.13
a
Isolated yields.
With the conditions we used for aryl nitriles, the R,â-
unsaturated nitriles can be converted to the correspond-
ing cyclopropylamines. Representative examples are
shown in Table 2. The reaction employing (E)-cinnamoni-
trile and (E)-2-decenenitrile proceeded smoothly to afford
the cyclopropylamines 7a and 7b in satisfactory yields
and without isomerization of the double bond (entries 1
and 2). Starting from 3-(2-furyl)acrylonitrile (6c), how-
ever, the yield was lower, possibly due to the instability
of the product (entry 3). 2,3-Substituted alkenenitriles
6d and 6e reacted in a similar way (entries 4 and 5).
In summary, we have presented an easy preparation
of primary 1-arylcyclopropylamines from readily avail-
able and cheap starting materials and reagents. More-
over, this method provides rapid access to 1-alkenylcy-
clopropylamines. The synthetic potential of these com-
pounds is currently studied in our laboratory.
SCHEME 3
general, as shown in Table 1. The cyclopropanation
occurred smoothly with the acceptor as well as the alkyl-
substituted nitriles (entries 2, 3, 5, 6, and 8). Starting
from the donor-substituted nitriles, however, the yield
depends on the substitution pattern, o- and p-methoxy
substituted benzonitriles giving lower yields than the
m-methoxy substituted benzonitrile (entries 1 and 7 vs
4). Isomeric 1-naphthyl cyclopropylamines 3j,k were
obtained in comparable yields (entres 9-10). A sterically
crowded cyanide, i.e., 2,4,6-trimethylbenzonitrile, could
also be used, but the yield was low (15%).
Exp er im en ta l Section 15
Starting from ethyl o-cyanobenzoate (4),11 the spiro-
cyclic lactam 5 was directly obtained, via a cyclopropa-
nation-lactamization sequence (Scheme 3). This reaction
was best performed at room temperature. As observed
for aliphatic â-cyanoesters, the addition of a Lewis acid
is not required.3c Several natural and synthetic isoindo-
lin-1-one moieties are biologically active products.12 The
presented method thus provides easy access to the
analogues bearing a cyclopropane ring.
Gen er a l P r oced u r e for th e Syn th esis of Cyclop r op yl-
a m in es 3a -k a n d 7a -e. Ethylmagnesium bromide (2.2 mmol,
1 to 2 M in ether) was added at -70 °C to a solution of a nitrile
(1 mmol) and Ti(Oi-Pr)4 (0.33 mL, 1.1 mmol) in Et2O (5 mL).
The yellow solution was stirred for 10 min. After the solution
was warmed to rt (1 h), BF3‚OEt2 (0.25 mL, 2 mmol) was added.
After the mixture was stirred for 1 h, 1 N HCl (ca. 3 mL) and
ether (ca. 15 mL) were added. NaOH (10% aq, ca. 10 mL) was
added to the resulting two clear phases and the mixture was
When higher Grignard reagents were used, 1,2-
substituted cyclopropylamines were formed albeit in low
yield. For example, a 25% yield of 2-ethyl-1-phenylcyclo-
propylamine was obtained from benzonitrile and either
n-BuMgBr or s-BuMgBr.
(13) (a) Aufranc, P.; Ollivier, J .; Stolle, A.; Bremer, C.; Es-Sayed,
M.; de Meijere, A.; Salau¨n, J . Tetrahedron Lett. 1993, 34, 4193-4196.
(b) Atlan, V.; Racouchot, S.; Rubin, M.; Bremer, C.; Ollivier, J .; de
Meijere, A.; Salau¨n, J . Tetrahedron: Asymmetry 1998, 9, 1131-1135.
(c) Racouchot, S.; Ollivier, J .; Salau¨n, J . Synlett 2000, 1729-1732. (d)
Racouchot, S.; Sylvestre, I.; Ollivier, J .; Kozyrkov, Y. Y.; Pukin, A.;
Kulinkovich, O. G.; Salau¨n, J . Eur. J . Org. Chem. 2002, 2160-2176.
(14) The Ti(II)-mediated conversion of amides into tertiary cyclo-
propylamines has never been applied to synthesize vinylcyclopropy-
lamines, see ref 7. Similarly, unsaturated esters did not convert
efficiently to vinylcyclopropanols, see ref 13d.
(11) Nitrile 4 was prepared from phthalic anhydride according to:
Carpino, L. A. J . Am. Chem. Soc. 1962, 84, 2196-2201.
(12) Kundu, N. G.; Wahab Khan, M. Tetrahedron 2000, 56, 4777-
4792 and references therein.
(15) For general experimental methods, see ref 3b.
7134 J . Org. Chem., Vol. 68, No. 18, 2003

extracted with ether. The combined ether layers were dried
(Na2SO4), filtered, and concentrated under reduced pressure. The
residue was purified by flash chromatography on silica gel
(Et2O).
(100), 148 (50). Anal. Calcd for C10H13NO‚HCl: C, 60.15; H, 7.07;
N, 7.01. Found: C, 59.95; H, 7.45; N, 6.84.
1-(2-Br om op h en yl)cyclop r op yla m in e (3i). Colorless oil;
1
71% yield (151 mg); IR (neat) 3370, 1588, 1564, 1468 cm-1; H
1-P h en ylcyclop r op yla m in e (3a ).8,16 Colorless oil; 65% yield
NMR (250 MHz, CDCl3) δ 0.88-0.93 (m, 2 H), 1.05-1.11 (m, 2
H), 2.09 (br s, 2 H), 7.10 (td, J ) 7.8, 1.8 Hz, 1 H), 7.24 (td, J )
7.6, 1.1 Hz, 1 H), 7. 35 (dd, J ) 7.6, 1.8 Hz, 1 H), 7.56 (dd, J )
7.8, 1.1 Hz, 1 H); 13C NMR (63 MHz, CDCl3) δ 15.3, 38.6, 125.3,
127.4, 128.3, 130.1, 133.0, 144.4; MS m/z (%) 213 (M+•, 12), 212
(98), 211 (M+•, 26), 210 (100). Anal. Calcd for C9H10BrN‚HCl:
C, 43.49; H, 4.46; N, 5.64. Found: C, 43.84; H, 4.23; N, 5.62.
1-(1-Na p h th yl)cyclop r op yla m in e (3j).8 Pale yellow oil; 57%
(87 mg); IR (neat) 3365, 1601, 1496, 1454 cm-1 1H NMR (250
;
MHz, CDCl3) δ 0.94-1.10 (m, 4 H), 1.96 (br s, 2 H), 7.14-7.35
(m, 5 H); 13C NMR (63 MHz, CDCl3) δ 17.8, 36.7, 125.3, 125.9,
128.3, 146.9; MS m/z (%) 133 (M+•, 16), 162 (78), 134 (100). Anal.
Calcd for C9H11N‚HCl: C, 63.72; H, 7.13; N, 8.26. Found: C,
63.57; H, 7.16; N, 7.90.
1-(4-Meth oxyp h en yl)cyclop r op yla m in e (3b).17 Pale yellow
oil; 43% yield (70 mg); IR (neat) 3366, 1513 cm-1; 1H NMR (250
MHz, CDCl3) δ 0.85-1.00 (m, 4 H), 1.86 (br s, 2 H), 3.75 (s, 3
H), 6.84 (d, J ) 8.9 Hz, 2 H), 7.23 (d, J ) 8.9 Hz, 2 H); 13C NMR
(63 MHz, CDCl3) δ 16.9, 36.4, 55.2, 113.6, 126.8, 139.0, 157.8;
MS m/z (%) 163 (M+•, 16), 162 (78), 134 (100). Anal. Calcd for
1
yield (104 mg); IR (neat) 3363, 1594, 1508 cm-1; H NMR (250
MHz, CDCl3) δ 1.00-1.07 (m, 2 H), 1.16-1.23 (m, 2 H), 1.95 (br
s, 2 H), 7.37-7.63 (m, 4 H), 7.76 (d, J ) 8.1 Hz, 1 H), 7.90 (d, J
) 8.0 Hz, 1 H), 8.45 (d, J ) 8.3 Hz, 1 H); 13C NMR (63 MHz,
CDCl3) δ 14.7, 36.3, 124.1, 125.2, 125.5, 125.6, 126.0, 127.5,
128.8, 131.5, 134.1, 141.9; MS m/z (%) 183 (M+•, 34), 182 (100),
154 (50). Anal. Calcd for C13H13N‚HCl: C, 71.07; H, 6.42; N, 6.38.
Found: C, 70.93; H, 6.40; N, 6.28.
C
10H13NO‚HCl: C, 60.15; H, 7.07; N, 7.01. Found: C, 59.87; H,
7.20; N, 6.82.
1-(4-Meth ylp h en yl)cyclop r op yla m in e (3c).8 White solid;
73% yield (107 mg); mp 92-94 °C; IR (neat) 3364, 1515, 1451
cm-1; 1H NMR (250 MHz, CDCl3) δ 0.91-1.04 (m, 4 H), 1.88 (br
s, 2 H), 2.33 (s, 3 H), 7.12 (d, J ) 8.1 Hz, 2 H), 7.24 (d, J ) 8.1
Hz, 2 H); 13C NMR (63 MHz, CDCl3) δ 17.3, 20.8, 36.4, 125.3,
128.9, 135.4, 143.8; MS m/z (%) 147 (M+•, 15), 146 (89), 132 (100),
118 (94). Anal. Calcd for C10H13N‚HCl: C, 65.39; H, 7.68; N, 7.63.
Found: C, 65.35; H, 7.87; N, 7.44.
1-(2-Na p h th yl)cyclop r op yla m in e (3k ). Pale yellow oil; 57%
1
yield (104 mg); IR (neat) 3377, 1631, 1598 cm-1; H NMR (250
MHz, CDCl3) δ 1.01-1.11 (m, 4 H), 1.92 (br s, 2 H), 7.24 (d, J )
8.6 Hz, 1 H), 7.33-7.48 (m, 2 H), 7.70-7.78 (m, 4 H); 13C NMR
(63 MHz, CDCl3) δ 17.7, 36.7, 123.4, 123.9, 125.2, 126.0, 127.3,
127.5, 128.0, 131.7, 133.1, 144.1; MS m/z (%) 183 (M+•, 50), 182
(100), 154 (92). Anal. Calcd for C13H13N‚HCl: C, 71.07; H, 6.42;
N, 6.38. Found: C, 70.83; H, 6.31; N, 6.31.
1-(4-F lu or op h en yl)cyclop r op yla m in e (3d ).8 Pale yellow
Spir o[cyclopr opan e-1,3′-(2′,3′-dih ydr o-1′-isoin dolon e)] (5).
Ethylmagnesium bromide (2.0 mmol, 1 to 2 M in ether) was
added at rt to a solution of 4 (1 mmol) and Ti(Oi-Pr)4 (0.33 mL,
1.1 mmol) in Et2O (5 mL). After the mixture was stirred for 1 h,
1 N HCl (ca. 3 mL) and CH2Cl2 (ca. 15 mL) were added. The
mixture was then extracted with CH2Cl2. The combined organic
layers were dried (Na2SO4), filtered, and concentrated under
reduced pressure. The residue was purified by flash chroma-
tography on silica gel (CH2Cl2-acetone 8:2) giving 5 as a white
solid; 73% yield (116 mg); mp 164-166 °C; IR (KBr) 3188, 1707,
oil; 64% yield (94 mg); IR (neat) 3363, 1601, 1511, 1223 cm-1
;
1H NMR (250 MHz, CDCl3) δ 0.89-1.06 (m, 4 H), 1.86 (br s, 2
H), 6.96 (t, J ) 8.7 Hz, 2 H), 7.25 (dd, J ) 8.7, 5.4 Hz, 2 H); 13
C
NMR (63 MHz, CDCl3) δ 17.3, 36.9, 114,7 (d, J C-F ) 21.0 Hz),
127.1 (d, J C-F ) 7.5 Hz), 142.5, 161.1 (d, J C-F ) 243.9 Hz); 19F
NMR (235 MHz, CDCl3) δ -117.7 (tt, J ) 8.5, 5.4 Hz); MS m/z
(%) 151 (M+•, 32), 150 (100), 122 (87). Anal. Calcd for C9H10FN‚
HCl: C, 57.61; H, 5.91; N, 7.46. Found: C, 57.56; H, 5.69; N,
7.33.
1-(3-Meth oxyp h en yl)cyclop r op yla m in e (3e). Colorless oil;
1650 cm-1 1H NMR (250 MHz, CDCl3) δ 1.42-1.68 (m, 4 H),
;
1
73% yield (119 mg); IR (neat) 3365, 1603, 1581 cm-1; H NMR
7.08 (d, J ) 7.6 Hz, 1 H), 7.44 (t, J ) 7.5 Hz, 1 H), 7.88 (t, J )
7.3 Hz, 1 H), 7.88 (d, J ) 7.3 Hz, 1 H), 8.38 (br s, 1 H); 13C NMR
(250 MHz, CDCl3) δ 13.6, 41.8, 117.8, 123.5, 127.0, 131.6, 131.8,
148.7, 171.2. Anal. Calcd for C10H9NO: C, 75.45; H, 5.70; N,
8.80. Found: C, 75.11; H, 5.76; N, 8.69.
(250 MHz, CDCl3) δ 0.95-1.10 (m, 4 H), 1.90 (br s, 2 H), 3.79 (s,
3 H), 6.72 (dd, J ) 8.2, 2.2 Hz, 1 H), 6.82-6.88 (m, 2 H), 7.22 (t,
J ) 8.2 Hz, 1 H); 13C NMR (63 MHz, CDCl3) δ 17.9, 36.5, 55.0,
110.8, 111.4, 117.5, 129.2, 148.7, 159.5; MS m/z (%) 163 (M+•
,
18), 162 (76), 134 (68), 132 (100). Anal. Calcd for C10H13NO‚
HCl: C, 60.15; H, 7.07; N, 7.01. Found: C, 60.36; H, 7.25; N,
6.98.
1-(2-P h en ylvin yl)cyclop r op yla m in e (7a ).13a Colorless oil;
65% yield (103 mg); IR (neat) 3367, 1645, 1600, 1493, 1448 cm-1
;
1H NMR (250 MHz, CDCl3) δ 0.74-0.81 (m, 2 H), 0.94-1.01 (m,
2 H), 1.76 (br s, 2 H), 5.94 (d, J ) 15.9 Hz, 1 H), 6.46 (d, J )
15.9 Hz, 1 H), 7.11-7.32 (m, 5 H); 13C NMR (63 MHz, CDCl3) δ
17.3, 35.5, 125.2, 125.7, 126.6, 128.4, 137.2, 138.1; MS m/z (%)
159 (M+•, 25), 158 (100), 130 (51). Anal. Calcd for C11H13N‚HCl:
C, 67.51; H, 7.21; N, 7.16. Found: C, 67.12; H, 7.18; N, 7.11.
1-(1-Non en yl)cyclop r op yla m in e (7b). Colorless oil; 50%
1-(3-Ch lor op h en yl)cyclop r op yla m in e (3f). Colorless oil;
1
72% yield (122 mg); IR (neat) 3371, 1597, 1569 cm-1; H NMR
(250 MHz, CDCl3) δ 0.91-1.10 (m, 4 H), 1.91 (br s, 2 H), 7.09-
7.30 (m, 4 H); 13C NMR (63 MHz, CDCl3) δ 18.3, 36.3, 123.2,
125.5, 125.8, 129.5, 134.1, 149.1; MS m/z (%) 168 (M - H, 19),
166 (M - H, 56), 140 (28), 138 (78), 132 (95), 75 (100). Anal.
Calcd for C9H10ClN‚HCl: C, 52.96; H, 5.43; N, 6.86. Found: C,
53.10; H, 5.42; N, 6.83.
yield (91 mg); IR (neat) 3370, 1466 cm-1 1H NMR (250 MHz,
;
CDCl3) δ 0.55-0.61 (m, 2 H), 0.79-0.90 (m, 5 H), 1.18-1.35 (m,
10 H), 1.71 (br s, 2 H), 2.02 (q, J ) 6.7 Hz, 2 H), 5.20 (d, J )
15.4 Hz, 1 H), 5.51 (dt, J ) 15.4, 6.7 Hz, 1 H); 13C NMR (63
MHz, CDCl3) δ 14.0, 16.3, 22.6, 29.1, 29.1, 29.7, 31.8, 32.1, 34.7,
125.9, 137.2; MS m/z (%) 181 (M+•, 6), 152 (20), 110 (67), 82 (100),
130 (51). Anal. Calcd for C12H23N: C, 79.49; H, 12.79. Found:
C, 79.55; H, 13.17.
1-(3-Br om op h en yl)cyclop r op yla m in e (3g). Colorless oil;
1
76% yield (161 mg); IR (neat) 3373, 1594, 1564 cm-1; H NMR
(250 MHz, CDCl3) δ 0.92-1.12 (m, 4 H), 1.82 (br s, 2 H), 7.10-
7.18 (m, 2 H), 7.25-7.33 (m, 1 H), 7.42-7.45 (m, 1 H); 13C NMR
(63 MHz, CDCl3) δ 18.2, 36.2, 122.4, 123.6, 128.4, 128.7, 129.7,
149.4; MS m/z (%) 212 (M - H, 23), 210 (M - H, 26), 184 (48),
182 (47), 132 (100). Anal. Calcd for C9H10BrN‚HCl: C, 43.49;
H, 4.46; N, 5.64. Found: C, 43.34; H, 4.47; N, 5.40.
1-(2-Meth oxyp h en yl)cyclop r op yla m in e (3h ).8 White solid;
58% yield (95 mg); mp 47-48 °C; IR (KBr) 3338, 1599, 1582,
1490, 1232 cm-1; 1H NMR (250 MHz, CDCl3) δ 0.79-0.93 (m, 4
H), 2.12 (br s, 2 H), 3.89 (s, 3 H), 6.84-6.89 (m, 2 H), 7.18-7.23
(m, 2 H); 13C NMR (63 MHz, CDCl3) δ 13.9, 34.8, 55.1, 110.3,
120.1, 127.8, 127.9, 133.9, 158.4; MS m/z (%) 163 (M+•, 14), 162
1-[2-(2-F u r a n yl)vin yl]cyclop r op yla m in e (7c). Orange oil;
42% yield (63 mg); IR (neat) 3358, 1656, 1601, 1491, 1150 cm-1
;
1H NMR (250 MHz, CDCl3) δ 0.75-0.81 (m, 2 H), 0.94-1.00 (m,
2 H), 1.75 (br s, 2 H), 5.94 (dd, J ) 15.8, 1.0 Hz, 1 H), 6.14 (d,
J ) 2.8 Hz, 1 H), 6.30-6.36 (m, 2 H), 7.29 (s, 1 H); 13C NMR (63
MHz, CDCl3) δ 17.5, 35.4, 105.9, 111.2, 114.2, 137.2, 141.1, 153.0;
MS m/z (%) 149 (M+•, 37), 148 (37), 121 (38), 120 (100). Anal.
Calcd for C9H11NO‚HCl: C, 58.23; H, 6.52; N, 7.54. Found: C,
58.28; H, 6.41; N, 7.26.
1-(1-Meth yl-2-p h en ylvin yl)cyclop r op yla m in e (7d ). Pale
yellow oil; 46% yield (80 mg); IR (neat) 3369, 1632, 1600, 1492,
(16) (a) Bunce, S. C.; Cloke, J . B. J . Am. Chem. Soc. 1954, 76, 2244-
2248. (b) Bonnekessel, J .; Ru¨chardt, C. Chem. Ber. 1973, 106, 2890-
2903.
1444 cm-1 1H NMR (250 MHz, CDCl3) δ 0.80-0.86 (m, 4 H),
;
(17) Harnisch, J .; Szeimies, G. Chem. Ber. 1979, 112, 3914-3933.
1.82 (br s, 2 H), 1.86 (s, 3 H), 6.52 (s, 1 H), 7.18-7.34 (m, 5 H);
J . Org. Chem, Vol. 68, No. 18, 2003 7135

13C NMR (63 MHz, CDCl3) δ 14.6, 15.2, 40.3, 123.9, 126.0, 128.0,
128.8, 138.2, 141.5; MS m/z (%) 173 (M+•, 19), 172 (74), 158 (100),
115 (98). Anal. Calcd for C12H15N‚HCl: C, 68.73; H, 7.69; N, 6.68.
Found: C, 68.80; H, 7.82; N, 6.72.
(%) 177 (M+•, 3), 176 (4), 162 (12), 136 (60), 108 (100). Anal. Calcd
for C12H19N‚HCl: C, 67.43; H, 9.43; N, 6.55. Found: C, 67.29;
H, 9.47; N, 6.49.
1-(6,6-Dim et h ylb icyclo[3.1.1]h ep t -2-en yl)cyclop r op yl-
a m in e (7e). Colorless oil; 62% yield (110 mg); IR (neat) 3365,
Su p p or tin g In for m a tion Ava ila ble: 1H spectra for com-
pounds 7a -e and 13C spectra for compounds 3e-g, 3i, 3k , 5,
and 7a -e. This material is available free of charge via the
Internet at http://pubs.acs.org.
1637 cm-1 1H NMR (250 MHz, CDCl3) δ 0.62-0.67 (m, 4 H),
;
0.79 (s, 3 H), 1.12 (d, J ) 8.6 Hz, 1 H), 1.28 (s, 3 H), 1.71 (br s,
2 H), 1.94 (br t, J ) 5.6 Hz, 1 H), 2.05-2.14 (m, 1 H), 2.22-2.42
(m, 3 H), 5.36-5.41 (m, 1 H); 13C NMR (63 MHz, CDCl3) δ 12.7,
21.1, 26.2, 31.0, 31.5, 36.6, 37.6, 40.7, 42.9, 114.1, 151.3; MS m/z
J O034710+
7136 J . Org. Chem., Vol. 68, No. 18, 2003